Evidence is accumulating which indicates that certain normal serum proteins such as transferrin bind to specific sites on several cell types potentially involved in immune responses. Thus, the human trophoblast, which is a fetal tissue and foreign to the mother, and certain tumors bind transferrin; similar binding sites may be expressed on peripheral blood lymphocytes when they become activated. The objectives of this project are, therefore, to perform basic studies of transferrin-binding reactions in these tissues and to initiate experiments to determine the possible biological role of such membrane binding sites. Cells will be investigated by combined radiolabel-binding and immunocytochemical methods, and the effects of defined inhibitors of DNA, RNA and protein synthesis, and enzymatic treatment with proteases and phospholipases also will be studied. Binding sites will be isolated to obtain basic physicochemical information and for use in preparation of antisera. The effects on transferrin-binding of complex formation with metallic cations such as iron or zinc also will be studied. In addition, the uptake of each cation will be examined with particular reference to the effects of metabolic and cytoskeletal inhibitors which affect temperature-dependent membrane ability and endocytosis of ligand-occupied structures.